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Herbsttagung der Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie Regensburg mit wissenschaftlicher Unterstützung der ADANO 2011

Arbeitsgemeinschaft Deutschsprachiger Audiologen und Neurootologen der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie (ADANO)

29.09. - 30.09.2011, Regensburg

The Next Generation in Genetic Hearing Loss Testing

Meeting Abstract

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  • author Heidi L. Rehm - Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, Pathology, Harvard Medical School, Boston, MA
  • Amy Lovelette Hernandez - Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, Otolaryngology and Communication Enhancement, Children's Hospital, Boston, MA
  • Margaret A. Kenna - Otolaryngology and Communication Enhancement, Children's Hospital, Boston, MA
  • Birgit H. Funke - Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, Pathology, Harvard Medical School, Boston, MA

Arbeitsgemeinschaft Deutschsprachiger Audiologen und Neurootologen der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Herbsttagung der Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie Regensburg mit wissenschaftlicher Unterstützung der ADANO 2011. Regensburg, 29.-30.09.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11adano13

DOI: 10.3205/11adano13, URN: urn:nbn:de:0183-11adano136

Veröffentlicht: 21. September 2011

© 2011 Rehm et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

The OtoChipTM Test sequences 19 genes involved in nonsyndromic and syndromic hearing loss: GJB2 (except 35delG), GJB6, MTRNR1, MTTS1, SLC26A4, OTOF, MYO6, TMPRSS3, TMIE, TMC1, MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, DFNB31, GPR98 (partial), and CLRN1. The test uses a combination of triplicate oligo hybridization sequencing and indel genotyping. We analyzed the first 150 OtoChipTM cases performed in our clinical lab. Twenty-three were excluded from analysis because of phenotypes inconsistent with the primary recommended indications (unilateral hearing loss-6, conductive/mixed hearing loss-5, CT abnormalities-8, auditory neuropathy-1 , non-Usher syndromic features-2 or unaffected-1). Of the 127 remaining cases, 97 had NSSNHL and 30 had eye findings suspicious for Usher syndrome. The majority of individuals (52.8%) were White with 11% Hispanic, 7.1% Asian, 3.9% Black, 2.4% Ashkenazi Jewish, 7.9% multi-racial, and 15% unspecified. From the 127 included cases, 21% were positive, 39% were inconclusive and 40% negative. This data is also broken down by phenotype at the time of testing (NSSNHL versus suspected Usher syndrome) as shown in Table 1 [Tab. 1]. Of the 27 positive cases, 7 patients had NSSNHL (tested at 0.4, 0.5, 1, 1, 2, 3, 5yrs) but have mutations in genes associated with Usher syndrome. Therefore, a conservative estimate of the rate of Usher syndrome among patients with apparent NSSNHL who test negative for GJB2 mutations is at least 7/88 (8%). Given the number of inconclusive cases and an incomplete sensitivity of the OtoChip for identifying all causes of Usher syndrome, the actual estimate is likely higher. For those cases with apparent NSSNHL and pathogenic mutations Type 1 Usher syndrome genes, it was interesting that hearing loss was often not profound. In summary, after connexin testing, the OtoChipTM is currently the most comprehensive single genetic test clinically available to identify a genetic etiology for hearing loss or Usher syndrome. I will also report on the development of our OtoGenome Test that will be launched in 2011 using our NextGen sequencing platform. The OtoGenome Test will cover all identified nonsyndromic hearing loss genes as well as genes associated with Usher, Pendred, and several other syndromes.